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Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on viable embryonated eggs of the whipworm Trichuris suis as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The applicant proposes to use the NF as a food supplement in the format of a 15-mL bottle containing 250 viable embryonated eggs of T .  suis . The target population for the NF is the general population. Considering the compositional data and proposed conditions of use, the consumption of the NF is considered of no nutritional relevance. Available data suggest that most larvae of T .  suis after hatching in the intestinal tract of humans remain immature and live for several weeks in the gastrointestinal tract of the human host. Nevertheless, under certain circumstances, T .  suis can be invasive in human, being able to mature into adult size and reproduce in humans. Human studies have also shown that administration of T .  suis ova may increase the incidence of adverse gastrointestinal reactions. The Panel considers that there are no studies available that demonstrate the safety of this NF intended for the general population at a proposed intake of 250 viable embryonated eggs of T .  suis ova per day. Based on the available information, the Panel cannot establish a safe dose at which no safety concerns would be expected. The Panel concludes that the safety of the NF has not been established., (© 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Following an application from Essential Sterolin Products (Pty) Ltd., submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of the Netherlands, the European Food Safety Authority (EFSA) Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to a combination of beta-sitosterol and beta-sitosterol glucoside and normal function of the immune system. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is a combination of beta-sitosterol and beta-sitosterol glucoside in a ratio 100:1. The Panel considers that a combination of beta-sitosterol and beta-sitosterol glucoside in a ratio 100:1 is sufficiently characterised. The claimed effect proposed by the applicant is 'normal function of the immune system by restoring balance between T H 1-T H 2 mediated immunity'. The Panel notes that the claimed effect 'normal function of the immune system by restoring balance between T H 1- and T H 2-mediated immunity' does not refer to a specific function of the body which can be assessed in vivo in humans by generally accepted methods, but rather to a mechanism of action by which the food/constituent could exert the claimed effect. The Panel considers that the claimed effect does not refer to any specific health claim as required by Regulation (EC) No 1924/2006. The Panel concludes that a cause and effect relationship cannot be established between the consumption of a combination of beta-sitosterol and beta-sitosterol glucoside in a ratio 100:1 and a beneficial physiological effect., (© 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on phenylcapsaicin as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Phenylcapsaicin is a chemically synthesised analogue of capsaicin intended to be marketed in food supplements and in foods for special medical purposes to the general population above the age of 11 years old at a maximum level of 2.5 mg/day. The highest intake of the NF is 2.5 mg/day which corresponds to 36 μg/kg body weight (bw) per day for adults, and 58 μg/kg bw per day for adolescents (10-14 years). The Panel considers that there is no concern with respect to genotoxicity of the NF. The reference point derived based on a 13-week rat study was the lowest of the model averaged BMDL 20 values of 37.2 mg/kg bw per day in females for increased plasma alanine aminotransferase (ALAT) levels. The Panel concludes that the NF, phenylcapsaicin, is safe under the proposed uses and use levels., (© 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel foods and Food Allergens (NDA) was asked to deliver an opinion on chia seeds ( Salvia hispanica L.) powders as novel foods (NFs) pursuant to Regulation (EU) 2015/2283. The NFs are partially defatted chia seed powders, obtained by extrusion of whole seeds of S. hispanica L. with the main differences between two powders in particle sizes and the content of some macronutrients. The information provided on the production processes, composition, batch-to-batch variability, stability and specifications of the NFs is sufficient and does not raise safety concerns. The applicant proposed to market the NFs as food supplements and as ingredients in a variety of foods. The target population for the NFs is the general population. Noting that no hazard raising safety concerns (except for allergenicity) could be identified from the information available on the source (i.e. chia seeds), the production processes, composition, specifications and proposed uses of the NFs, irrespectively of the maximum use levels at the proposed uses, the Panel considers that intake estimates and additional toxicological data for the NFs are not needed for this assessment. The Panel concludes that the NFs, partially defatted powders of whole chia seeds, are safe under the assessed conditions of use., (© 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 2'-fucosyllactose/difucosyllactose (2'-FL/DFL) mixture as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is a powdered mixture mainly composed of two oligosaccharides, 2'-FL and DFL, which are produced together by fermentation with a genetically modified strain of Escherichia coli K12. The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF in a variety of foods, including infant and follow-on formula, foods for infants and young children, foods for special medical purposes and food supplements. The target population is the general population except for food supplements, for which the target population is individuals above 1 year of age. Since the intake of 2'-FL and DFL from the NF at the proposed use levels is unlikely to exceed the intake level of naturally occurring 2'-FL and DFL in breastfed infants per kilogram body weight, the Panel concludes that the NF, a mixture of 2'-FL and DFL, is safe under the proposed conditions of use for the proposed target population., (© 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Following an application from analyze & realize GmbH submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Ireland, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to GlycoLite™. The Panel considers that the food, an aqueous extract from white kidney bean ( Phaseolus vulgaris L.) standardised by its in vitro α-amylase inhibitory activity (GlycoLite™) which is the subject of the health claim, is sufficiently characterised. The claimed effect proposed by the applicant is 'helps to reduce body weight'. The proposed target population is 'overweight people from the age of 18 years who want to lose or manage their weight'. The Panel considers that a reduction in body weight is a beneficial physiological effect for overweight individuals. Two human intervention studies, carried out in the same centres and by the same research group, showed an effect of 3 g of GlycoLite™ on body weight when consumed daily for 12 weeks in the context of an energy restricted diet. The results have not been replicated in a different setting. One study of short duration and methodological limitations showed an effect of GlycoLite™ on body weight when eating ad libitum . No evidence for a plausible mechanism by which GlycoLite™ could exert a reduction in body weight in vivo in humans has been provided. The Panel concludes that the evidence provided is insufficient to establish a cause and effect relationship between the consumption of an aqueous extract from white kidney bean ( P. vulgaris L.) standardised by its in vitro α-amylase inhibitory activity (GlycoLite™) and a reduction of body weight either under energy restriction or when eating ad libitum ., (© 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel foods and Food Allergens (NDA) was asked to deliver an opinion on overall safety assessment for chia seeds ( Salvia hispanica L.) as a novel food (NF) pursuant to Regulation (EU) 2015/2283 in the light of the increasing dietary intake from the growing number of authorised uses in recent years. The safety assessment of this NF is based on data supplied in seven applications, previous safety assessments of chia seeds and information retrieved from an extensive literature search done by EFSA. Since none of the applications addressed the possible formation of process contaminants, the present assessment is limited to those proposed extended uses which do not raise safety concerns regarding the formation of such contaminants. These include the use of whole and ground chia seeds added to chocolate, fruit spreads, fruit desserts, mixed fruit with coconut milk in twin pot, fruit-preparations to underlay a dairy product, fruit-preparations to be mixed with dairy products, confectionary (excluding chewing gums), dairy products and analogues, edible ices, fruit and vegetables products, non-alcoholic beverages and compotes from fruit and/or vegetables and/or with cereals. In addition, this assessment also concerns uses of chia seeds without specific restrictions and precautions regarding their use levels in other foods which usually do not include heat treatment during processing and cooking. Apart from allergenicity, the Panel did not identify any hazard which causes safety concerns. Lacking the basis and need to establish safe maximum intake levels for chia seeds, no exposure assessment was conducted. The Panel concludes that chia seeds are safe under the assessed conditions of use., (© 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Following an application from H.J. Heinz Supply Chain Europe B.V. submitted for authorisation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of the Netherlands, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to Nutrimune and immune defence against pathogens in the gastrointestinal (GI) tract and upper respiratory tract (URT). The food Nutrimune (a pasteurised cow's skim milk fermented with Lactobacillus paracasei CBA L74) which is the subject of the health claim is sufficiently characterised. The Panel considers that immune defence against pathogens in GI tract and URT is a beneficial physiological effect. Two human intervention studies were submitted as being pertinent to the claim, which were evaluated by the Panel in the previous application. One human intervention study from which conclusions could be drawn showed an effect of Nutrimune on immune defence against pathogens in the GI tract and the URT. The post hoc re-analysis of the two human studies combined does not address the methodological limitations of the second study raised in the previous opinion, i.e. that the study was not planned, designed, randomised and analysed as a multicentre study, and that the large disparity of subjects in the three centres was not duly justified. The results from one animal study could support an effect of Nutrimune on defence against pathogens in the GI tract. No evidence was provided for a plausible mechanism by which Nutrimune could exert the claimed effect in vivo in humans. The Panel concludes that the evidence provided is insufficient to establish a cause and effect relationship between the consumption of Nutrimune and immune defence against pathogens in the GI tract and URT., (© 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

In 2018, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) concluded that whey basic protein isolate obtained by ion exchange chromatography from skimmed cow's milk is safe for human consumption under the proposed conditions of use as infant and follow on formula, meal replacement beverages, foods for special medical purposes and food supplements. Following a request from the European Commission, the EFSA NDA Panel was asked to deliver a scientific opinion on whey basic protein isolate for extended uses in foods for special medical purposes and food supplements for infants as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The applicant seeks to extend the conditions of use to infant (powder 30 mg/100 g and reconstituted 3.9 mg/100 mL) and follow on formulae (powdered 30 mg/100 g and reconstituted 4.2 mg/100 mL) as foods for special medical purposes as well as in food supplements for infants (25 mg/day). The Panel considers that the proposed extended uses would not increase the potential intake of the NF compared to that assessed in its 2018 opinion. The Panel concludes that whey basic protein isolate is safe at the extended uses and use levels., (© 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

In 2017, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) concluded that betaine as a novel food (NF) is safe to be used at a maximum intake level of 6 mg/kg body weight per day in addition to the intake from the background diet. Following the present request from the European Commission, the EFSA NDA Panel was asked to deliver a scientific opinion on betaine by carrying out the assessment for the revised uses and use levels of betaine as proposed by the applicant. Thus, EFSA performed an intake assessment based on individual data from the EFSA Comprehensive European Food Consumption Database and the new proposed uses of the NF for the general population. The resulting ranges for the mean and high-level estimated intakes of betaine for the general population do not exceed the safe level of intake previously established. The Panel concludes that the NF, betaine, is safe under the new proposed conditions of use., (© 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on Yarrowia lipolytica yeast biomass as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is the dried and heat-killed biomass of Yarrowia lipolytica , a yeast species that is widespread in nature and which can be found in the environment as well as in foods. The production process is sufficiently described and does not raise safety concerns. The information provided on the composition of the NF is sufficient and does not raise safety concerns. The applicant proposed to use the NF as a food supplement in the form of capsules, tablets or powder. The target population for the NF is the general population above 3 years of age. The maximum proposed daily use levels are 3 g/day for children from 3 years to less than 10 years of age and 6 g/day thereafter. Taking into account the composition of the NF and the proposed use levels, the consumption of the NF is not nutritionally disadvantageous. No relevant toxicological information was provided. The Panel considers that given the qualified presumption of safety (QPS) status for production purposes of Yarrowia lipolytica and the fact that the production process of the NF does not raise safety concerns, no toxicological studies are needed for the safety assessment of the NF. The Panel concludes that the NF, Yarrowia lipolytica yeast biomass, is safe under the proposed conditions of use., (© 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Introduction: Chronic spontaneous urticaria (CSU) in childhood affects the quality of life of the patient and may be associated with other autoimmune diseases. The aim of this study was to investigate the association of autoimmune diseases with CSU in children., Methods: In a 3-year period, from 2015 to 2018, forty-nine children were diagnosed with CSU and monitored in the Outpatient Pediatric Allergy Clinic of the University Hospital of Ioannina in Northwestern Greece. The comorbidity with other autoimmune diseases was investigated in this population by autoantibody evaluation., Results: Of the 49 children with CSU, 1 had autoantibodies for celiac disease (CD), which was confirmed by duodenal biopsy via gastroscopy. Four children had high serum levels of anti-thyroid peroxidase antibodies but normal thyroid function. No other specific autoantibodies were detected., Conclusion: The prevalence of autoimmune diseases among our children with CSU was low. Nevertheless, we think it is important to test children with CSU for other autoimmune diseases. CD can be diagnosed in children with CSU even in the absence of other indicative signs., (© 2019 S. Karger AG, Basel.)

In 2018, the EFSA NDA Panel adopted the Scientific Opinion on the safety of d-ribose as a novel food pursuant to Regulation (EU) 2015/2283 when used in a variety of food, concluding that d-ribose is safe for the general population at intake levels up to 36 mg/kg body weight (bw) per day, but that its safety at the intended uses and use levels as proposed by the applicant could not be established. Following a request from the European Commission, the EFSA NDA Panel was asked to carry out a supplementary safety assessment for d-ribose by considering the new proposed uses and use levels submitted by the applicant. In order to address the present mandate, an intake assessment was carried out based on individual data from the EFSA Comprehensive European Food Consumption Database. Intakes were estimated for all age groups of the general population. The resulting ranges for the mean and high-level estimated intakes of d-ribose for all the population groups, including the target population groups, did not exceed the acceptable level of intake for the general population previously defined, i.e. 36 mg/kg bw per day, except for one survey on adolescents where the mean and 95th percentile of the intake estimates were 8.6 and 39.4 mg/kg bw per day, respectively. The Panel concludes that the novel food, d-ribose, is safe under the new proposed conditions of use., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The present scientific opinion deals with the assessment of the bioavailability of magnesium, from the proposed nutrient source, magnesium citrate malate (MgCM), when added for nutritional purposes to food supplements. MgCM is a mixed salt consisting of magnesium cations and citrate and malate anions, and with a magnesium content of 12-15%. MgCM is proposed to be used in food supplements that are intended to provide up to 300-540 mg/day magnesium. The data provided demonstrate that the production process results in batches of MgCM that comply with the product specifications and that the product is stable throughout its proposed shelf life. The human studies provided demonstrate that magnesium from MgCM is bioavailable. However, the extent of its bioavailability per se or compared to other magnesium sources cannot be established due to the lack of an appropriate magnesium source as a comparator in the studies provided or relevant kinetic data for magnesium. One publication provided in the dossier reported that supplementation with MgCM decreases calcium absorption, but this finding was not supported by publications on different magnesium salts and therefore the Panel could not draw conclusions from this finding. The Panel concludes that MgCM is a source from which magnesium is bioavailable, but the extent of its bioavailability cannot be established. The Panel notes that at the proposed maximum use levels of MgCM, the existing tolerable upper intake level for magnesium in nutritional supplements, water, or added to food and beverages (250 mg/day) is exceeded., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

EFSA has asked the Panel on Nutrition, Novel Foods and Food Allergens (NDA) to update the guidance on the scientific requirements for health claims related to physical performance published in 2012. The update takes into account the experience gained by the NDA Panel with the evaluation of additional health claim applications, changes introduced to the general scientific guidance for stakeholders for health claims applications and information collected from a grant launched in 2014 which aimed at gathering information in relation to claimed effects, outcome variables and methods of measurement in the context of the scientific substantiation of health claims. The guidance is intended to assist applicants in preparing applications for the authorisation of health claims related to muscle function and physical performance. The draft guidance was subject to public consultation from 16 July to 2 September 2018. This document supersedes the guidance on the scientific requirements for health claims related to physical performance published in 2012. It is intended that the guidance will be further updated as appropriate in the light of experience gained from the evaluation of health claims., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Purpose of Review: To present the most recent evidence on beta-lactam hypersensitivity reactions in children., Recent Findings: Drug provocation tests (DPTs) are the gold standard when investigating beta-lactam allergy in children and evidence is increasingly supporting DPTs without skin tests as a safe approach when evaluating children with nonimmediate mild reactions to beta-lactams. Of note, data are limited in the adolescent population, and this attitude may not apply to this age group. Standardization of DPT protocols is required in nonimmediate reactions, as many protocols ranging from 1 to 10 days have been described. The optimal duration of DPT is still unknown, with extended protocols providing slightly more sensitivity and possible higher long-term compliance, at the expense of potential side effects associated with prolonged antibiotic use. On the other hand, 1-day DPTs will identify the vast majority of patients, and the rest will only develop a mild rash during a subsequent full treatment. The natural history of beta-lactam allergy in children is not well studied with recent evidence pointing to the resolution of most confirmed beta-lactam allergies after 3 years., Summary: Further studies are needed for the standardization of DPT protocols and to confirm the favourable natural history of beta-lactam drug allergies in children. In addition, multicentric studies are required to confirm the increasingly accepted position of performing DPTs without skin tests in nonimmediate mild reactions to beta-lactams and to further evaluate the possibility of performing DPTs in benign immediate reactions to beta-lactams in children.

Competing Interests: Authors have no conflicts of interest.

Background and Objectives: Maternal prenatal stress (MPS) may result in a range of longterm consequences in the offspring among which there is susceptibility to allergic diseases. This review presents the current knowledge on the pathways through which MPS may affect the fetus, and the existing evidence regarding the association between MPS and development of allergy in the offspring., Result and Discussion: A pivotal mediator triggered in response to stress is the release of glucocorticoids (GC). GC may affect gene expression through binding to GC receptors, thus affecting fetal development in general, and allergic vulnerability in particular. A series of recent findings also indicate that MPS may affect the fetus programming of immune functions and lead to vulnerability of the immune system. MPS may hinder the gradual process in the offspring's cytokine production towards a Th1 type immune response. Prenatal factors may also influence the intrauterine microbiome and thereby the maternal bacteria transferred into the fetal gastrointestinal tract. The imbalances of intestinal microbiota in infancy could result in deviations in the development of systemic immune function, predisposing to allergic sensitization. Epidemiological studies in humans also suggest that there is an association of MPS and allergic vulnerability of the offspring., Conclusion: Although the existing evidence support a relationship of MPS with allergic predisposition of the offspring, further studies are needed to elucidate whether the association is dependent on the type of stress and whether it involves any type of allergic predisposition or not., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Emerging evidence indicate that maternal prenatal stress (MPS) can result in a range of long-term adverse effects in the offspring. The underlying mechanism of MPS is not fully understood. However, its complexity is emphasized by the number of purportedly involved pathways namely, placental deregulated metabolism of maternal steroids, impaired maturation of fetal HPA axis, imbalanced efflux of commensal bacteria across the placenta, and skewed immune development toward Th2. Fetal programming probably exerts a pivotal role in the end result of the above pathways through the modulation of gene expression. In this review, we highlight the current knowledge from epidemiological and experimental studies regarding the effects of MPS on asthma development in the offspring.

Various additives, including food colorants (FCs), are used in the food industry to make food appealing to consumers and to add variety. Despite the widespread usage of FCs, adverse reactions related to their consumption, including reactions triggered by immune (immediate and delayed-type hypersensitivity) and non-immune (intolerance) mechanisms, are considered rare. There is a discrepancy between the perception of patients and parents (7.4%) and the reported prevalence of adverse reactions to additives (0.01-0.23%), which is higher in atopic individuals (2-7%). Documented reactions are mild, involving mainly the skin, and, rarely, anaphylaxis. A major problem in diagnosing reactions to FCs is identification of the offending agent(s), which is based on careful dietary history taking. Allergy testing is usually unrevealing, except for reaction to some natural colorants. Treatment consists of avoidance of the offending colorant as no successful desensitization procedures have been reported., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the insulin resistance status in SGA infants at 12 months and its relationship with auxological and metabolic parameters., Methods: One group of 45 SGA and one of 50 appropriate for gestational age infants were followed from birth to the end of the first year of life. At 12 months, skinfold thickness, waist circumference, and blood levels of glucose, insulin, adiponectin, leptin, resistin, visfatin, retinol-binding protein 4, IGFs, lipids profile were determined, and the HOMA-IR index was calculated., Results: The SGAs had increased insulin (5.2 ± 2.7 versus 2.9 ± 2.4 μIU/ml, p = 0.012) and HOMA-IR (1.09 ± 0.9 versus 0.59 ± 0.55, p = 0.016). In multiple regression, insulin resistance indices were independently correlated with low-birth-weight (β = -2.92, p = 0.015 for insulin, β = -2.98, p = 0.011 for HOMA-IR) but not with catch-up growth in either height or weight or any other metabolic parameter. Resistin was higher in the SGAs (5.1 ± 2.1 versus 3.9 ± 2.1 ng/ml, p = 0.03) and independently correlated with low-birth-weight but not insulin resistance. Resistin was negatively correlated with total cholesterol (R = -0.33, p = 0.007) and positively with lipoprotein(a) (R = 0.49, p = 0.001)., Conclusion: Low-birth-weight, but not catch-up growth or adiposity tissue hormones, was correlated with insulin resistance at 12 months in non-obese SGA infants. The higher resistin in SGA infants and its correlation with total cholesterol and lipoprotein(a) need further clarification.

The burden of asthma in childhood is considerable worldwide, although some populations are much more affected than others. Many attempts have been made by different investigators to identify the factors that could predict asthma development or persistence in childhood. In this review, the relation between atopic sensitization as an indicator of allergy and asthma in childhood will be discussed. Cross sectional studies, carried out in different countries, failed to show any firm correlation between asthma and atopic sensitization. Birth cohort mainly of infants at high risk for asthma and case-control studies showed that atopic sensitization was a risk factor for current asthma in children older than 6 years. In general, clear relations are observed mostly in affluent Western countries, whereas in less affluent countries, the picture is more heterogeneous. For the prediction of asthma development or persistence in school age children, other prerequisites should also be fulfilled such as family history of asthma and wheezing episodes at preschool age. Despite the conductance of different studies regarding the potential role of allergen avoidance for the primary prevention of childhood asthma, it does not seem that this approach is of benefit for primary prevention purposes. However, the identification of children at risk for asthma is of benefit as these subjects could be provided with the best management practices and with the appropriate secondary prevention measures.

Asthma and allergy share a similar and very close course, especially through childhood. Considerable research effort has been put in untangling these associations; however, it is now becoming obvious that this is an exceedingly difficult task. In fact, each research breakthrough further perplexes this picture, as we are steadily moving toward the era of personalized medicine and we begin to appreciate that what we thought to be a single disease, asthma, is in fact an accumulation of distinct entities. In the context of this "syndrome," which is characterized by several, as of yet poorly defined endotypes and phenotypes, the question of the link of "asthma" with allergy probably becomes non-relevant. In this review, we will revisit this question while putting the emphasis on the multifaceted nature of asthma.

This review presents up-to-date understanding of immunotherapy in the treatment of children with allergic asthma. The principal types of allergen immunotherapy (AIT) are subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). Both of them are indicated for patients with allergic rhinitis and/or asthma, who have evidence of clinically relevant allergen-specific IgE, and significant symptoms despite reasonable avoidance measures and/or maximal medical therapy. Studies have shown a significant decrease in asthma symptom scores and in the use of rescue medication, and a preventive effect on asthma onset. Although the safety profile of SLIT appears to be better than SCIT, the results of some studies and meta-analyses suggest that the efficacy of SCIT is better and that SCIT has an earlier onset than SLIT in children with allergic asthma. Severe, not controlled asthma, and medical error were the most frequent causes of SCIT-induced adverse events.

Food protein-induced proctocolitis (FPIP) is the most common colonic manifestation of food allergy in infants, accounting for up to 60% of exclusively breast-fed children. The causative foods derived from the mother's diet, which are then excreted in her milk. The suggested risk factors for the development of FPIP are an immature immune system, altered intestinal permeability and other factors that activate local immune function, such as genetic susceptibility in combination with particularly sensitizing foods. FPIP is an enhanced immune responsiveness of some infants to very small amounts of food antigens, inducing an inflammatory mucosal response, mediated by T cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objective: Clarify the frequency and the pathophysiological mechanisms of the rare manifestations of Epstein-Barr virus infection., Sources: Original research studies published in English between 1985 and 2015 were selected through a computer-assisted literature search (PubMed and Scopus). Computer searches used combinations of key words relating to "EBV infections" and "atypical manifestation.", Summary of the Findings: Epstein-Barr virus is a herpes virus responsible for a lifelong latent infection in almost every adult. The primary infection concerns mostly children and presents with the clinical syndrome of infectious mononucleosis. However, Epstein-Barr virus infection may exhibit numerous rare, atypical and threatening manifestations. It may cause secondary infections and various complications of the respiratory, cardiovascular, genitourinary, gastrointestinal, and nervous systems. Epstein-Barr virus also plays a significant role in pathogenesis of autoimmune diseases, allergies, and neoplasms, with Burkitt lymphoma as the main representative of the latter. The mechanisms of these manifestations are still unresolved. Therefore, the main suggestions are direct viral invasion and chronic immune response due to the reactivation of the latent state of the virus, or even various DNA mutations., Conclusions: Physicians should be cautious about uncommon presentations of the viral infection and consider EBV as a causative agent when they encounter similar clinical pictures., (Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

It is a great consensus in the scientific community that environmental factors, such as weather conditions and ambient air pollution, have vital impacts on respiratory diseases. Further, these factors imply the potential to have many significant impacts on aeroallergens, and therefore related diseases such as asthma and allergic rhinitis. The impacts are more pronounced in sensitive groups of population, such as children and elderly, living in urbanized areas. Over the last three decades, studies have shown changes in production, dispersion and allergen content of pollen and spores, which may be region- and species-specific. In addition, these changes may have been influenced by air pollutants interacting directly with pollen. It is not easy to evaluate the impact of climate change and air pollution on the prevalence of asthma in general and on the timing of asthma exacerbations. However, the global rise in asthma prevalence and severity suggests that air pollution and climate changes could be contributing. The objective of this review is to summarize the environmental impacts on pulmonary diseases in children based on recent literature over the world.

In as much as many infants develop allergic symptoms early in infancy, and exposure to allergens may be important in the development of food allergies, there is great interest in maternal dietary strategies during pregnancy and lactation that may prevent food allergies, and thus reduce the burden of disease. Vitamin D levels are known to be associated with atopic disease development in early infancy; however, existing data are controversial. The aim of this review was to investigate any possible effect of vitamin D on the onset of neonatal allergy via breast feeding.

Food protein-induced enterocolitis syndrome (FPIES) represents the severe end of the spectrum of gastrointestinal food hypersensitivity; its acute episodes can culminate in severe dehydration and hypovolemic shock, and its chronic form entails considerable morbidity associated with feeding difficulty and failure to thrive. Nevertheless, awareness for this syndrome remains rather low. Many factors hamper the establishment of FPIES diagnosis. Such factors pertain to the pathophysiological mechanism of the syndrome, causal food proteins, clinical manifestations, diagnostic procedures, differential diagnosis considerations, and prevailing perceptions which may require critical appraisal. Throughout this review, we will present and discuss these issues and put the focus on factors that could lead to under-diagnosis of FPIES, cause numerous acute episodes, and substantially increase the diseases morbidity and financial burden. We will also address other issues that are clinically relevant to FPIES., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Patients with moderate-to-severe allergic rhinitis who are inadequately controlled despite treatment according to current rhinitis management guidelines have a significant unmet medical need. Such patients have a negative impact on daily functioning and are at risk of developing serious comorbidities, such as asthma and chronic rhinosinusitis., Objective: To assess the efficacy and safety of omalizumab in poorly controlled allergic rhinitis under a meta-analysis framework., Methods: MEDLINE and the Cochrane Central Register of Controlled Trials were searched through September 2013. Studies on the efficacy of omalizumab in allergic rhinitis that assessed clinical outcomes were selected. Descriptive and quantitative information was extracted; mean differences and relative risk estimates were synthesized under a fixed or random effects model. Heterogeneity was assessed by using the Q statistic and the I(2) metric. Subgroup analyses were performed for the presence of specific immunotherapy treatment., Results: Of the 352 citations retrieved, 11 studies of 2870 patients were finally included. A statistically significant reduction in the daily nasal symptom severity score (standardized mean difference -0.67 [95% CI, -1.3 to -0.31]; P < .0001; I(2), 92%) and a statistically significant reduction in daily nasal rescue medication score (-0.22 [95% CI, -0.39 to -0.05; P = .01; I(2), 58%) were observed. There was not a statistically significant difference in the occurrence of any adverse event (relative risk 1.06 [95% CI, 0.94-1.19; I(2), 55%)., Conclusions: Omalizumab is statistically significantly associated with symptom relief, decreased rescue medication use, and improvement of quality of life in patients with inadequately controlled allergic rhinosinusitis., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Even though cow's milk protein allergy (CMPA) is one of the most common food allergies in childhood, its prognosis is generally good and cow's milk (CM) is usually reintroduced in the patient's diet. The natural history of CMPA shows heterogeneity and is closely related to the immunological and clinical phenotype by which CMPA presents. Children with non-IgE-mediated CMPA tend to develop tolerance at an earlier age and at a higher percentage compared to those with IgE-mediated disease. In subjects with severe symptoms CMPA may persist for longer or ever. Although, the majority of children will outgrow their allergy, the individual timing of tolerance acquisition is largely unknown. Most of the current guidelines on the diagnosis and management of CMPA suggest reevaluation of milk-allergic children every 6-12 months, and reintroduction of CM after a negative Oral Food Challenge (OFC). However, OFC procedure is time consuming, expensive and not without risk. Clinical variables and the measurements of sIgE levels and SPT wheal sizes to crude (whole) CM protein and individual milk protein components may provide some useful prognostic information in the course of CMPA. However, no clear-cut clinical or laboratory criteria exist to predict which children and at what age are more likely to pass a repeat (reintroduction) OFC. The identification of factors that could accurately predict the outcome of reintroduction OFC and the timing of tolerance development would be extremely useful in daily clinical practice. Until recently, reintroduction of CM was commonly attempted when children with CMPA were more likely to have become tolerant. Over the last years, a different approach in the management of milk and egg allergy has emerged with specific oral tolerance induction (SOTI) as a promising method for the treatment of food allergies. Furthermore, a number of studies have shown evidence that introduction of heated milk and egg protein into the diet of allergic patients may induce the acquisition of tolerance. Still, the question of when and how to reintroduce cow's milk in milk-allergic children remains challenging and further research in this important field is necessary to provide both clinicians and anxious parents with the desirable answer.

In this review, clinical and epidemiological aspects of milk allergy along with current data on the structure and function of the main cow's milk allergens, are presented. Milk allergy is the most frequent food allergy in childhood. One of the reasons why allergy to cow's milk shows its highest prevalence in children is its early introduction into the diets of infants when breast feeding is not possible. The major allergens are caseins, a-lactalbumin and β-lactoglobulin, but allergies to other minor proteins (immunoglobulins, bovine serum albumin) have also been reported. Milk allergenicity can be reduced by various processing methods (mainly hydrolysis), and processed formulas based on cow's milk can often be safely introduced to children allergic to milk proteins. Cross reactivity has been described between different mammalian milks and between milk and meat or animal dander.

There is increasing evidence that vitamin D regulates immune responses. There is also epidemiological evidence of a relationship between vitamin D deficiency and development of asthma. In addition, several epidemiological studies suggest that low levels of vitamin D during pregnancy and early life are inversely associated with the risk of developing respiratory infections and wheezing in childhood. Vitamin D also seems to reduce asthma exacerbation and increase the response to glucocorticoids. These findings have led to considering a possible link between the occurrence of allergic respiratory diseases and low levels of vitamin D. However, the precise role of vitamin D in the pathogenesis of asthma still remains unclear, emphasizing the need for well-designed trials on vitamin D supplementation to decipher its role in preventing and/or managing the disease. This review examines the relationship that exists between vitamin D deficiency and childhood wheezing and asthma.

The increased consumption of fish and shellfish has resulted in more frequent reports of adverse reactions to seafood, emphasizing the need for more specific diagnosis and treatment of this condition and exploring reasons for the persistence of this allergy. This review discusses interesting and new findings in the area of fish and shellfish allergy. New allergens and important potential cross-reacting allergens have been identified within the fish family and between shellfish, arachnids, and insects. The diagnostic approach may require prick to-prick tests using crude extracts of both raw and cooked forms of seafood for screening seafood sensitization before a food challenge or where food challenge is not feasible. Allergen-specific immunotherapy can be important; mutated less allergenic seafood proteins have been developed for this purpose. The persistence of allergy because of seafood proteins' resistance after rigorous treatment like cooking and extreme pH is well documented. Additionally, IgE antibodies from individuals with persistent allergy may be directed against different epitopes than those in patients with transient allergy. For a topic as important as this one, new areas of technological developments will likely have a significant impact, to provide more accurate methods of diagnosing useful information to patients about the likely course of their seafood allergy over the course of their childhood and beyond., (© 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)

Glutathione S-transferases (GSTs) are a group of enzymes involved in the detoxification process of carcinogens and other substances. The genes encoding isoenzymes M1 and T1 have "null" alleles, which are polymorphic in humans. Our purpose was to examine whether the GSTM1 and GSTT1 homozygous null genotypes have an impact on the response to recombinant human erythropoietin (rhuEpo) treatment in MDS patients. We analyzed lymphocyte DNA samples from 27 patients with all types of myelodysplastic syndromes (MDS) at the time of diagnosis. All patients were scheduled to receive rHuEpo in doses of 150 u/Kg/day for a period of 12 weeks in order to obtain and maintain stable responses. A multiplex polymerase chain reaction (PCR) was used to genotype both GSTM1 and GSTT1 simultaneously, in responders and non-responders to rhuEpo with respect to various pretreatment parameters: haemoglobin, white blood cell count, platelets, serum erythropoietin, transfusion requirements and bone marrow blasts. The data obtained were evaluated by chi2 test and odds ratio were extracted. Twelve out of 27 evaluated patients demonstrated an erythroid response (44%). Nine out of the 12 patients (75%) responding after 12 weeks of treatment had GSTM1 null genotype (OR=3.4). In contrast, only 1 responder (8.3%) was homozygotes of GSTT1 null genotype. Furthermore, no statistically significant difference in the response rate of the different MDS subgroups was observed. Our results suggest that a treatment with rHuEpo may be effective in achieving a stable erythroid response in MDS patients who carry an homozygous deletion of the GSTM1 gene.

Glutathione sulfur transferases (GSTs) is a group of enzymes involved in the detoxification process of carcinogens and other substances. The genes encoding isoenzymes M1 and T1 are polymorphic in humans and the phenotypic absence of enzyme activity (null genotype) may have an effect on the risk of chronic lymphoblastic leukemia (CLL). Our purpose was to examine whether the GSTM1 and GSTT1 homozygous null genotypes altered the risk of CLL. DNA was extracted from the peripheral blood of 27 patients with CLL and 147 cancer-free controls; both groups originated from a defined population (residents of the Ioannina region, northwestern Greece) and were similar with regard to mean age, race and sex; GSTM1 and GSTT1 were simultaneously analyzed by a multiplex polymerase chain reaction (PCR) method and Fisher's exact test was used for comparisons between the two groups. A significantly increased incidence of the GSTM1 null genotype was found in the group of patients compared to the controls (74.07 versus 34.69%, P = 0.0002). Additionally, the incidence of the GSTT1 null genotype was comparable in patients and controls (25.92 versus 10.20%, P = 0.05). The frequency of the combined GSTM1 null/T1 null genotype was significantly different between patients and controls (14.81 versus 2.04%, P = 0.012). However, there was no relationship between the advanced stage of the disease and the GSTs status. Individuals with the GSTM1 and GSTT1 null genotypes may have enhanced susceptibility to CLL.